Chronic pain is a ubiquitous, debilitating and costly affliction of both children and adults. Important aspects of pain-related behavior are mediated by supraspinal mechanisms. The rostral ventromedial medulla (RVM) has both anti- and pro-nociceptive modulatory capabilities, each referable to a distinct, physiologically identified cell class. "Off-cells" are proposed to inhibit, and "on-cells" to facilitate, nociceptive processing. The remaining RVM neurons, "neutral cells", do not alter their activity in relationship to nocifensive behavior, and their role in pain modulation is currently unclear. The proposed research will employ complementary electrophysiological and anatomical approaches (single cell recording and iontophoresis, juxtacellular labeling, and immunohistochemistry) to characterize the distribution of purinergic receptors on the three cell classes. With this information, I will directly and selectively manipulate the activity of each class in order to demonstrate a specific role in nociceptive modulation. My doctoral and post-doctoral research training has centered on the functional anatomy of brainstem catecholaminergic neurons and the neurochemistry of the basal forebrain and striatum. My clinical interest as an academic pediatric neurosurgeon is in functional nervous system diseases such as spasticity, medically refractory epilepsy and movement disorders. My goal is to develop scientific and clinical expertise in central nervous system electro physiology, enabling me to launch an independent and competitively funded laboratory and also to develop a clinical program of neuromodulatory treatment (deep brain stimulation) for movement disorders in children. Oregon Health & Sciences University is an ideal location to pursue these goals. The University is recognized as centers for excellence in neuroscience research and functional neurosurgery. My mentor, Dr. Mary Heinricher, is a well-established and highly productive basic researcher, and my institution has committed to my developing a formal program in functional pediatric neurological surgery, which will complement my basic investigational activities.